EPIDEMIOLOGY
Although lung cancer is a malignancy of
increasing age, with 70% of cases occur-
ring in over 65-year-olds, i...
be aspirated and washings, needle
aspiration or brushings obtained for
cytology with mucosal biopsies for
pathology. A par...
CLINICAL FEATURES
Less than 10% of patients are asympto-
matic at presentation. These cases are
often discovered as a resu...
57
Lung cancer II
• The most useful clinico-pathological
classification is into SCLC and
NSCLC.
• SCLC is an aggressive ce...
METASTATIC SPREAD AND THE
LUNG
HAEMATOGENOUS SPREAD
The lung, in receiving all of the cardiac
output, is a common site for...
distal to bronchial
obstruction. Sleeve
resection of the
bronchial wall with
the tumour should
be curative.
Histologically...
Intravascular thrombi originate in
systemic veins, usually in the deep veins
of the lower limb, and migrate into the
pulmo...
implications.
Further investigation can be directed
to either confirming the presence of deep
leg vein clot from which emb...
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Lung cancer primary and metastatic

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Lung Cancer

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Lung cancer primary and metastatic

  1. 1. EPIDEMIOLOGY Although lung cancer is a malignancy of increasing age, with 70% of cases occur- ring in over 65-year-olds, it represents a significant socio-medical burden. In the developed world it has become the com- monest cause of cancer death in men. In the UK it represents 1 in 3 cancer deaths and 25% of cancer registrations. In women it is the most rapidly rising cause of cancer mortality and is now second only to breast cancer. In Scotland it even exceeds breast cancer mortality, with lung cancer causing annually the loss of over 51 500 life-years compared with 21 000 life-years for breast cancer. PATHOGENESIS Tobacco The great potential for primary preven- tion in lung cancer is self-evident. Around 90% of lung cancer is attribut- able to cigarette smoking. Rates in men in the developed countries are falling slightly concomitant with reductions in smoking: in contrast to those seen in women. The evidence implicating pas- sive smoking in the genesis of lung tumours is not as robust. Very few patients (< 10%) are true ‘never smok- ers’. Tobacco smoke contains over 40 dif- ferent oxidants and carcinogens, includ- ing benzpyrenes, acrolein and benzene. In susceptible patients these cause neoplastic change at the bronchial epithelium. Despite exposure of the whole mucosa to inhaled compounds, the development of tumours is usually focal. The activation of tumour promoting genes and inhibition of tumour suppressor genes (including p53, see box) occurs. Depending on the host’s immunological response, cell reproduction may continue with this loss of normal cellular growth and differentia- tion mechanisms. This results in a macro- scopic tumour (Fig. 1). Hence, the substantial rise in lung cancer that we are still seeing reflects the widespread uptake of cigarette smoking earlier in the last century. Even a complete cessation now of smoking would take many years to see an effect on lung cancer. That only 20% of cigarette smokers develop lung cancer demonstrates the role of inter-individual factors that include: • Genetics. Non-smokers with a family history of lung cancer are at greater risk compared to non-smokers without a pedigree. • Environment. Rural populations usually have lower incidence rates than urban communities. • Social deprivation. Communities scoring highly for social deprivation show higher rates than less deprived areas, even when corrected for cigarette consumption. Deprivation may be a surrogate for factors such as dietary intake of antioxidant vitamins and minerals. Other causes Asbestos is an inert natural rock silicate with uses in industry. Unfortunately, it is also a carcinogen in its own right. The risk of exposure to asbestos is synergistic with tobacco smoke. To a non-smoker the risk of lung cancer from asbestos exposure is five times that of an unex- posed non-smoker, while in a smoking worker the exposure risk is 55 times that of an unexposed non-smoker. Other occu- pational causes of lung cancer include the inhalation of radioactive gases, including environmental exposure to radon, and workplace chemicals that include arsenic, chromate and those of the elec- tronics industries. CLINICAL PRESENTATION Clinical presentation is usually late in the tumour’s natural history. Furthermore, co-morbidity in an aged and largely uncomplaining group of patients con- tributes to the poor survival rates. Overall, a mere 8% of diagnosed patients will survive 5 years, a rate that has changed little in the past three decades. The current poor outlook for patients with this disease might be improved by a high index of clinical suspicion for ear- lier diagnosis to offer more patients potentially curative surgery. Barely 20% of patients at presentation have disease sufficiently localised for attempts at curative surgery. SCREENING The combination of a readily identifiable population at increased risk of develop- ing lung cancer and such poor survival due in part to late presentation would suggest a need for screening pro- grammes. However, programmes utilis- ing chest radiography and sputum cytology in a number of healthcare sys- tems around the world have been disap- pointing. There has been no objective evidence of a survival benefit in any of these screened populations. CLASSIFICATION Clinically and pathologically, it is useful to consider malignant lung tumours as either small (undifferentiated) cell lung LUNG CANCER I RESPIRATORY DISEASE 〉 NEOPLASTIC DISEASE54 Activation of tumour promoting genes Inactivation of suppressor genes Growth factors enhancing Host immune response Continued cell division and loss of differentiation New blood vessel strands Invasion and desimination Molecular changes Carcinoma in situ Invasive malignancy Fig. 1 The development of lung cancer. Fig. 2 Cytological examination of early morning sputum with malignant (orange and green staining) squamous cells. (Image courtesy of Dr G. Rebello.) selby pp54-59 18/4/02 7:22 AM Page 54
  2. 2. be aspirated and washings, needle aspiration or brushings obtained for cytology with mucosal biopsies for pathology. A partial assessment of the suitability of the patient for surgery can also be made. • Pleural aspiration and biopsy in the presence of pleural fluid and hence possible pleural deposits of tumour. • Needle aspiration of neck nodes for cytology. • Transthoracic needle aspiration or biopsy of subpleural masses (Fig. 4). • Thoracoscopy and biopsy of pleural, mediastinal or subpleural pulmonary masses. • Liver or bone biopsy of possible deposits. cancer (SCLC, about 20% of lung can- cers) or non-small cell lung cancer (NSCLC). SCLC This can be diagnosed with a high degree of confidence, even cytologically. It typi- cally presents as a bulky central lung tumour with early spread to mediastinum and to extrathoracic sites. The tumour cells proliferate rapidly and untreated patients have a median survival of a mere 3–4 months from presentation. NSCLC NSCLC covers a heterogeneous group. Pathologists recognise: • squamous cell carcinomas (now about 20–25%) • adenocarcinoma (40%) • undifferentiated (non-small cell) carcinomas • truly mixed tumours. These tumours may be more difficult to type with confidence on cytology or small biopsy specimens, hence the use- fulness of NSCLC as a classification. Adenocarcinomas have increased in fre- quency over the last 2–3 decades. In recent US and UK studies outside ethnic Chinese populations, adenocarci- noma is now the most common form of NSCLC. SCLC is also increasing as a proportion of all lung cancer. These changes may reflect the increase in women smokers and changes in the type and burning qualities of current tobacco. PATHOLOGICAL DIAGNOSIS The majority of patients need the clinical or radiological suspicion of lung cancer to be pathologically confirmed. There is always a balance between what is possi- 55 Lung cancer I • Lung cancer is the most common solid tumour affecting males in western Europe. • Tobacco smoking is the major and most easily preventable, but not the sole, risk factor. • Clinical presentation is often late; the diagnosis may not be readily apparent, a factor contributing to poor survival rates over the last three decades. p53 and cigarette smoke The human gene called p53 is a tumour suppressor gene that initiates programmed cell death in malignant cells. Specific point mutations in p53 preventing cell death are common in human cancers, particularly lung tumours. Tobacco smoke con- tains a carcinogen benzo[a]pyrene, a metabolite of which has been demonstrated to cause at least one of these specific mutational changes to p53 gene in a number of experimental cell types. There may well be other carcinogens which produce specific mutations in this or other tumour suppressor genes. This provides the first molecular evidence directly linking cigarette smoke with the genesis of lung cancer. Control of such gene activity may be an avenue for future anti-tumour therapies. LUNG CANCER I Case history 24 A 50-year-old man presents with pain in his left hip of gradual onset over days. He has a central mass on his chest radiograph. • How would you confirm your suspicion of lung cancer? • Why does he have bone pain? • Blood results demonstrate Na:122; Ca: 2.6; alb 34; alk phosphate: 650. Why? ble and what is therapeutically appropri- ate for an individual patient. Techniques available include: • Cytological examination of early morning sputum (Fig. 2). This may be more readily obtainable and is less invasive than bronchoscopy for central airway disease. Three adequate samples on consecutive mornings should be considered standard. • Flexible bronchoscopy for central endobronchial (Fig. 3) or peribronchial disease. Secretions can Fig. 4 CT guided needle biopsy of lung mass. Fig. 3 Flexible bronchoscopy. selby pp54-59 18/4/02 7:22 AM Page 55
  3. 3. CLINICAL FEATURES Less than 10% of patients are asympto- matic at presentation. These cases are often discovered as a result of a chest radiograph performed for another reason and usually present as a solitary periph- eral lesion (SPL). An SPL may be benign or malignant, primary or secondary (Fig. 1). Benign disease, especially tuberculo- sis granulomas or benign tumours, should always be considered. There are no radiological features absolutely char- acteristic of benignity, but the presence of certain patterns of calcification, occur- rence at the site of known benign disease and previous radiology demonstrating slow if any change in size are all helpful. An SPL is more likely to be malignant with increasing age of the patient, partic- ularly if a smoker. If there is a known primary tumour elsewhere, or there is clinical evidence of one, the SPL is likely to be a secondary. If the available evi- dence suggests a primary and the patient is fit, then curative resection should be planned. This will provide histological confirmation and potential cure at the same time. Such a policy accepts finite resection rates both for lesions that turn out to be benign (less than 5% and usually tuberculosis), and for those that with the passage of time become evident as sec- ondaries (up to 10% of adenocarcino- mas). Primary tumours Of the remaining presenta- tions, one-third have symp- toms due to the primary tumour. New cough or change in a long-standing cough, even without haemoptysis, is an important symptom in a smoker, even if a chest radi- ograph is normal. The conse- quences of large airway obstruction (Fig. 2) that may include inspiratory stridor, ‘slow to radiologically resolve’ pneumonia, undue or worsening breathlessness that may be difficult to distinguish from the many other causes. Metastases A further third of presentations are due to intrathoracic (Fig. 3) or extrathoracic (Fig. 4) metastases. Systemic symptoms The remaining patients present due to systemic symptoms. Weight loss may result from cytokines secreted by the tumour. Lassitude is also characteristic. Non-metastatic or para-neoplastic manifestations arise by the production of circulating factors derived from the primary tumour, and may be apparent at initial presentation or later. Treatment of the primary may not always alleviate these manifestations. The common pat- terns are: • Bone: —clubbing, rarely in SCLC —hypertrophic pulmonary osteoarthropathy, painful wrists and ankles from new bone formation, usually squamous or adenocarcinoma. • Endocrine: —ADH secretion, usually by SCLC causing hyponatraemia the commonest electrolyte upset; patients become confused, require fluid restriction and demeclocycline —non-metastatic hypercalcaemia, due to PTH-like substances secreted usually by squamous tumours —Cushing’s syndrome: rapid onset with weakness (myopathy and hypokalaemia) and hyperglycaemia from ectopic ACTH secretion. LUNG CANCER II RESPIRATORY DISEASE 〉 NEOPLASTIC DISEASE56 Fig. 1 Solitary peripheral lesion. Apical tumour and brachial plexus erosion; arm pain Rib deposit and pain Pleural effusion, breathlessness Phrenic nerve palsy and diaphragm elevation Hoarseness with recurrent laryngeal nerve palsy Lobar bronchus obstruction, lobe collapse, breathlessness, cough, haemoptysis Lymphangitis, breathlessness Pericardial infiltration, atrial fibrillation and tamponade Central tumour • stridor • SVC obstruction and face swelling Fig. 3 Intrathoracic spread of lung cancer with associated symptoms. Fig. 2 Airway obstruction by endobronchial tumour. selby pp54-59 18/4/02 7:22 AM Page 56
  4. 4. 57 Lung cancer II • The most useful clinico-pathological classification is into SCLC and NSCLC. • SCLC is an aggressive central tumour with a median survival of 3 months untreated. • For many patients, symptom control is the main therapeutic goal. LUNG CANCER II • Haematology: coagulopathy, disseminated intravascular coagulation with a consumptive bleeding disorder or venous thromboses and superficial phlebitis. • Neurology: rare syndromes in a spectrum from peripheral neuropathy through myaesthenia to dermatomyositis. MANAGEMENT Surgery Surgery for NSCLC, and probably for very early SCLC, still offers the best chance of cure, with a 5-year survival of 50% in early stage NSCLC. This requires a thorough clinical, laboratory and radio- logical assessment to ensure the patient is fit to withstand single-lung anaesthesia and major surgery, along with an absence of metastatic malignant disease outwith the planned resection of lobe or lung. This usually requires: • Pulmonary function to include FEV1 FVC, Kco, walking distance, resting electrocardiogram. Cardiac reserve may have to be assessed further with either an exercise treadmill test or coronary angiography. • Biochemistry including calcium and liver enzymes. • Plain radiology of chest. • CT scan of chest particularly to Case history 25 A 50-year-old man has a bone sec- ondary from lung cancer. Blood results demonstrate: calcium 2–7 mmol/l, albumin 34 g/l, alkaline phosphatase 650 u. What treatment could you offer? Table 1 Quality of life – symptom-relieving strategies in lung cancer Breathlessness Cough Pain Haemoptysis Identify and treat conventionally heart failure, COPD, anaemia, etc Pleural effusion • drain and pleurodese Lobar or main stem obstruction • radiotherapy endoluminal tumour ablation • tracheobronchial stent Lymphangitis • steroid trial Radiation pneumonitis • steroid trial ‘Tumour associated’ • breathing relaxation techniques • pacing activities • other non-pharmacological techniques such as aromatherapy and acupuncture • liquid morphine • nebulised morphine • anxiolytic Radiotherapy • external beam • intraluminal (brachytherapy) Endobrachial cautery argon plasma Bone pain • non-steroidal analgesic and opiate • radiotherapy Neural pain • steroid • anticonvulsant, e.g. gabapentin Anorexia, weight loss • small frequent meal • increase spice/herb use • steroid • anti-inflammatory drug Oral opiate Nebulised lignocaine (with care) identify mediastinal glands that should be sampled for histology. Many centres include CT of liver but ultrasound is at least as good as CT and liver deposits are unlikely in the absence of an elevated alkaline phosphatase. Thoracic surgical teams will formally explore the mediastinum to sample nodes directed by the CT scan before undertak- ing formal resection. Alternative therapies Surgical cure should be the goal in fit patients with resectable NSCLC. In patients with resectable disease, but who decline surgery or have intercurrent (usually cardiac) disease, radical radio- therapy may be an option with cure rates not that different from surgery. SCLC can be treated with cyclical combination chemotherapy, providing a median sur- vival of around 12 months with an increased quality of life. Palliative care Palliative care, in the broadest multidis- ciplinary sense, should begin at diagnosis and the breaking of that bad news to the patient. Radiotherapy can palliate the symptoms of bone pain, significant haemoptysis, breathlessness from lobe or lung collapse consequent on airway obstruction or impending collapse, supe- rior mediastinal obstruction and spinal cord compression. Radiotherapy offers little for the non-specific symptoms of lassitude and weight loss. New chemotherapy regimes even for inopera- ble NSCLC may help such symptoms. Control by pharmacological or non- pharmacological means of pain, cough and breathlessness in particular are impor- tant. Metabolic disturbances including hyponatraemia and hypercalcaemia can present insidiously, and should be actively sought. These will respond to appropriate therapy. Teflon injection of a paralysed vocal cord under local anaes- thetic can help voice quality. As survival is in general poor, the quality of life should be paramount in the management of such patients. Future therapies Advancements in understanding tumour development and cell biology will allow Brain • meningeal infiltration–headache • confusion • paresis • fits Cervical adenopathy Liver deposits • pain from capsule stretch • jaundice Adrenal deposits • common but rarely significant Bone deposits • pain • nerve entrapment including cord • pathological fracture • hypercalcaemia Fig. 4 Extrathoracic spread of lung cancer with associated symptoms. selby pp54-59 18/4/02 7:22 AM Page 57
  5. 5. METASTATIC SPREAD AND THE LUNG HAEMATOGENOUS SPREAD The lung, in receiving all of the cardiac output, is a common site for haematoge- nous tumour deposition, even secondary spread from a lung primary. Other com- mon primary sites include gut (stomach, rectal), genitourinary, breast and malig- nant melanoma (Fig. 1). Pulmonary deposits may be asymptomatic or appear before the primary is clinically apparent. Such haematogenous secondaries appear as discrete ‘cannon-ball’ masses enlarg- ing on chest radiographs over time (Fig. 2). They tend to be subpleural and lower zone. When small, secondaries need dif- ferentiation from benign granulomas on CT scanning. An isolated metastasis requires differentiation from a primary lung tumour. A solitary secondary may be considered for metastectomy either for relief of symptoms or as a debulking procedure. There may be a worthwhile time delay before further secondaries develop. Any other treatment must be governed by the primary tumour. PLEURAL DEPOSITS Pleural tumour deposits present as pleural effusions, rarely as discrete pleural masses. Investigation by Abrams biopsy or thoracoscopy should confirm the diagnosis. Stomach, breast and ovar- ian tumours often spread to the pleura, with therapeutic gain in discovering pri- rigid by a lattice-work of tumour within the lymphatics. If performed, CT scan- ning will demonstrate nodules of tumour along a pattern of distended lymphatics. ENDOBRONCHIAL SECONDARIES These metastases that occur on the luminal side of the bronchi are rare. Those that occur in the central airways and, hence, are visible at bronchoscopy represent about 1 per 150 bronchoscopies for cancer (Fig. 4). Most are found as an explanation for haemoptysis or obstructing symptoms. Often there is a past history of the primary cancer; colon and breast are the most common (Fig. 5). RARE TUMOURS Bronchioloalveolar cell carcinoma This is a form of adenocarcinoma that has a propensity for spread along the alveolar walls and into lymphatics. Insidious breathlessness, a cough pro- ductive of frothy sputum and a progres- sive pneumonia-like illness are usual presentations. Chest radiology demon- strates alveolar shadowing (Fig. 6). Cytology of sputum or bronchoscopic washings will confirm malignancy and bronchoscopic lung biopsy may demon- strate the characteristic pattern of alveo- lar wall spread. Often at diagnosis METASTATIC SPREAD AND THE LUNG RESPIRATORY DISEASE 〉 NEOPLASTIC DISEASE58 Fig. 1 Haematogenous spread: whole lung pathology (a) and chest X-ray (b) of an individual with malignant melanoma metastases in the lung. (b)(a) Fig. 2 Multiple, mainly peripheral and variable in size — these are the characteristic features of multiple blood-borne lung metastases. mary tumours in the latter two sites (see pp. 66–67). INTERSTITIAL LYMPHATIC SPREAD Lymphangitis carcinomatosis has a sug- gestive radiological pattern of progres- sive interstitial shadowing, including septal and intrapulmonary (Kerley A) lymphatic lines (Fig. 3). The clinical pic- ture is of a patient, usually with a known primary, complaining of relentless breathlessness. Their distress is often seemingly out of proportion to the appar- ent plain X-ray abnormalities, but reflects the increasingly stiff lungs held selby pp54-59 18/4/02 7:22 AM Page 58
  6. 6. distal to bronchial obstruction. Sleeve resection of the bronchial wall with the tumour should be curative. Histologically, ‘atypical carcinoids’ may present as above but tend to behave more as malignant tumours with local and distant spread. They are chemosensi- tive. There is some morphological and embryological basis in considering a spectrum of behaviour from typical car- cinoid through ‘atypical’ to small cell lung tumours. Lymphangioleiomyomatosis (LAM) This is a malignancy of immature pul- monary smooth muscle cells and is believed to originate from the lymphat- ics. Infiltration of bronchioles leads to focal emphysema contralateral lung is involved preventing attempts at curative surgery. Chemo- therapy is of limited benefit. The dis- tressing symptoms of cough and breath- lessness need palliation. Bronchial carcinoid This is the commonest benign lung tumour. Embryologically it is derived from fore-gut neuroendocrine cells. It very rarely presents as the carcinoid syn- drome of flushing and diarrhoea (in con- trast to mid gut carcinoid tumours with hepatic metastases). Biologically, there is a spectrum of behaviours. The ‘typical’ carcinoid tumours are vascular endobronchial polypoid tumours that present usually in young women as either recurrent haemoptysis or recurrent infections with radiological infiltrates 59 Metastatic spread and the lung • The lung and pleura are common sites for metastatic tumour deposition. METASTATIC SPREAD AND THE LUNG Fig. 3 Interstitial lymphatic spread: chest X-ray. Fig. 6 Alveolar shadowing of bronchioalveolar cell carcinoma. Fig. 4 Endobronchial deposit. This lady presented with haempotysis and a normal chest radiograph. Biopsy confirmed mucin-secreting adenocarcinoma, histologically similar to colonic cancer removed 4 years previously. Haematogenous spread Large deposits (e.g. from renal, melanoma) Miliary small deposits (e.g. from thyroid carcinoma) Pleural deposits (often with fluid) • adenocarcinoma • breast • ovary • gut • lung Endobronchial deposits • colon • breast Lymphangitic spread Fig. 5 Metastatic spread to the lungs – common primary sites. and air trapping. Veno-occlusion and lymphatic involvement contributes to the clinical picture. It occurs almost exclu- sively in women of reproductive age, and growth seems dependent on oestrogen hormones. Presentation is in early to middle adult life with breathlessness and airflow limitation. Frequent complications include haemoptysis, pneumothorax or chylous effusions. The chest radiograph will show a reticular pattern to the lung parenchyma. High-resolution CT lung scanning will demonstrate thin-walled cystic airspaces. Treatment is supportive with progesterone until a menopause. selby pp54-59 18/4/02 7:22 AM Page 59
  7. 7. Intravascular thrombi originate in systemic veins, usually in the deep veins of the lower limb, and migrate into the pulmonary circulation. They are rela- tively frequent within hospitalised patients, can be difficult to diagnose and yet fatal. Several studies have demon- strated prevalences in a hospitalised pop- ulation of venous clot ranging from less than 10% when associated with minor medical illness to exceeding 70% follow- ing surgery for traumatic hip fractures. Embolism into the pulmonary circulation may cause 10% of all hospital deaths. MECHANISMS Intravascular thrombus formation usually starts in the deep venous system of the calf. This is called a ‘deep vein thrombo- sis’ (DVT). The mechanisms that prevent the formation and propagation of intra- vascular thrombus fail as a result of: • Abnormal or damaged vascular endothelium, especially important for arterial thrombosis and within grafts, less of a factor in calf veins except in recurrent venous thrombosis. • Blood stasis or pooling, usually resulting from immobility. Immobility is the most prevalent predisposing factor, closely followed by the cause of the immobility. Trauma, following surgery, and many medical illnesses are associated with an acute inflammatory response that leads to the following. • Imbalance between the blood’s pro- coagulant and thrombolytic properties that favours coagulation. Conditions include malignancy, particularly disseminated adenocarcinomas, therapy with oestrogens either as contraceptives or hormone replacement, or the antiphospholipid antibody syndrome. Moreover rare inherited deficiencies of particular fibrinolytic proteins can favour a procoagulant tendency. DEEP CALF VEIN THROMBOSIS Often such clot is clinically silent though localised calf discomfort, swelling and warmth may occur. Such features are not diagnostic but are more likely when clot propogates proximally into the thigh veins. It is this proximal extension that is most at risk of embolising. The presence of clot should be actively confirmed or excluded by radiological investigation. The two most available imaging investi- gations are: • Lower limb ascending venography. This is considered to be the gold standard investigation. The technique uses intravenous contrast to radiologically outline the deep venous system of the legs from calf extending proximally into femoral and iliac vessels. Thrombus is demonstrated as consistent filling defects within the outlined vessels. The technique involves radiation exposure and the slight risk of reaction to the radio-opaque contrast used. • Doppler ultrasound examination of the veins. This utilises the demonstration of a Doppler signal by flowing blood with the deep veins. The absence of a spontaneous flow signal in non-compressible veins can be taken as evidence of occlusive thrombus. Although it is less sensitive than venography in imaging the calf veins, it is as good from popliteal to iliac vessels. Being free of ionising radiation, such examinations can readily be repeated if clinical circumstances require. Deep venous clot proximal to the calf is treated with anticoagulant therapy to prevent further extension, traditionally heparin alone or followed by warfarin. During such therapy the existing clot will be lysed by endogenous systems. This recanalisation is at the expense of losing the competence of venous valves. The long term sequelae of such venous incompetence includes the ‘post- phlebitic’ leg with chronic swelling, pain and ulceration. There is some evidence that treatment by thrombolysis (rather than anticoagulant therapy) and long- term wearing of support hosiery may reduce this complication. PULMONARY EMBOLI (PE) Proximal leg vein thrombus may break off and travel through the right heart with the potential there for outflow obstruction, before lodging and occlud- ing part of the pulmonary vascular bed. The consequences of such acute emboli- sation are: • Breathlessness due to the loss of pulmonary vascular bed but without the degree of localised circulatory compromise that results in lung infarction. There may be few clinical signs. • Pulmonary infarction syndrome with sudden onset pleurisy and cough often productive of blood with undue breathlessness. Clinical signs may include localised crackles, pleural fluid and occasionally a pleural rub. Chest radiographs may show the development of intrapulmonary pleural-based shadowing with pleural fluid. • Sudden collapse as a result of substantial clot causing obstruction to the outflow tract of the right ventricle or a major pulmonary artery. The symptoms may not be immediately recognised for what they represent: acute central chest pain, breathlessness and circulatory collapse, systemic hypotension but with distended neck veins: a ‘right heart syndrome’. Death may ensue. Substantial loss of the pulmonary vascular bed occurs but the cardiovascular effects are more than the mere consequences of vascular bed loss. Right ventricular and even left ventricular dysfunction with the release of vasoactive inflammatory mediators as a result of the intravascular clot is as important. In contrast, closing the vascular supply to one lung surgically, or by vessel occlusion with inert material, causes only transient haemodynamic effects. Repeated embolisation of clot to the pulmonary circulation over days to weeks can lead to the syndrome of ‘cor pulmonale’ with breathlessness, hypoxia, right heart strain and fluid retention. Clinical features The clinical features of pulmonary embolism are non-specific. There are few other potentially lethal conditions for which our clinical diagnostic accuracy is so poor. In an acutely ill or post-operative patient there are a number of other diag- nostic possibilities, including pneumo- nia. The entire clinical picture including an assessment of risk supplemented by chest radiography, electrocardiography and arterial blood gases can provide a feel for the likelihood of a pulmonary embolus or the possibility of an alternate diagnosis. Further investigation has to be performed to confirm or refute the diag- nosis of pulmonary emboli because of the potential lethality and the therapeutic PULMONARY THROMBOEMBOLI RESPIRATORY DISEASE 〉 PULMONARY VASCULAR DISEASE60 selby pp60-63 18/4/02 7:24 AM Page 60
  8. 8. implications. Further investigation can be directed to either confirming the presence of deep leg vein clot from which embolisation was possible, or confirming pulmonary embolisation. The pulmonary arterial circulation can be imaged at pulmonary angiography where clot can be visualised as filling defects (Fig. 1). This is the probably the definitive investigation but is not always available. Isotope lung scanning provides a simpler means to image lung perfusion (Fig. 2) but interpretation of such scans is not always easy and over-interpretation is a risk. About 60% of lung scans are unhelpful in either confirming or refuting pulmonary embolism as the diagnosis. In such cases additional imaging is required which may include leg vein imaging. Echocardiography is often readily avail- able, can demonstrate acute right heart strain with pulmonary hypertension and helps to exclude other causes of an acute right heart syndrome. Alternative tech- niques include helical CT scanning with contrast (p. 77) and magnetic resonance imaging; both techniques may be useful in demonstrating large pulmonary vessel clot. Management Anticoagulant therapy is the mainstay of treatment. It should be commenced once the diagnosis is suspected, as long as there are no contraindications to such therapy. Once anticoagulant therapy is commenced, mortality falls to less than 10%. Unfortunately, only 10% of deaths attributed to PE received any such treat- ment prior to death. Anticoagulant therapy should be commenced as heparin, and warfarin is then started. Heparin can be discontinued once the effect of warfarin is therapeutic. Heparin alone is used in the later stages of pregnancy, but with the added risks of immune thrombocytopenia and of osteo- porosis with such long-term therapy. Recurrent embolisation that continues from leg vein clot once anticoagulation is established requires consideration of an inferior vena caval interruption device. This is usually a ‘caval filter’, an umbrella net that is placed percuta- neously and acts truly as a filter. The role of thrombolysis in acute massive PE associated with major haemodynamic upset is still controversial but may be lifesaving. The most efficient way to prevent both fatal and non-fatal pulmonary emboli and DVT is aggressive prophy- laxis in at-risk hospital patients. This can be achieved using mechanical techniques including early mobilisation and leg compression devices. Subcutaneous heparin as the low molecular weight heparins now available are effective and simple to use. No technique is com- pletely reliable in preventing pulmonary emboli. Miscellaneous sources of thrombotic pulmonary emboli These are summarised in Figure 3. There are rare sources of pulmonary emboli that should be considered in any of the pulmonary thromboembolism syndromes when leg vein clot is demonstrably absent. These include: • Clot from the right heart including mural thrombus in dilated right Pulmonary thromboemboli • Pulmonary embolisation is potentially lethal and often complicates hospitalisation and major illness. • It can be difficult to diagnose, with patients receiving risky therapy when they have not suffered the condition and other patients going untreated for an undiagnosed life-threatening condition. • Clinical assessment alone is insufficient for diagnosis or upon which to base long- term treatment decisions. Radiological imaging is essential to confirm the diagnosis. • Preventative therapy, whether physical or pharmacological, is the most cost-effective. 61 Case history 26 A 30-year-old female on the oral contraceptive pill with a history of poorly controlled asthma presents with rapid onset severe breath- lessness and pleurisy. A chest radiograph is normal. Having started treatment for pulmonary emboli, how could you confirm your suspicions? PULMONARY THROMBOEMBOLI Fig. 1 Pulmonary artery clot demonstrated by contrast angiogram. Fig. 2 Isotope perfusion lung scan illustrating impaired delivery to left upper and right lower lung regions. These perfusion defects represent vascular bed obstruction from emboli (chest radiograph normal). Fig. 3 Miscellaneous sources of thrombotic pulmonary emboli. Tumour along vein Thrombus, often infected on central venous catheter Right axial myxoma Right ventricular mural thrombus, following infarction or when dilated and poorly functioning Amyloid kidney, renal vein thrombosis Renal carcinoma with tumour extension along or in situ thrombosis Pelvic vein clot ventricles. • Embolisation from the renal veins can occur. The material is either tumour spreading directly along the renal vein or renal vein thrombosis especially in amyloidosis. • Right heart myxomas are exceptionally rare. selby pp60-63 18/4/02 7:24 AM Page 61

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